Serotonin, a neurotransmitter with mixed and complex pharmacological characteristics, was first discovered in 1948 and subsequently has been the subject of an immense quantity of research. Serotonin, also referred to as 5-hydroxytryptamine (5-HT), acts both centrally and peripherally on discrete 5-HT receptors. Current dogma delineates 5-HT receptors into three major subclassifications--5-HT.sub.1, 5-HT.sub.2 and 5-HT.sub.3 --each of which may also be heterogeneous.
Molecules which selectively interact with the serotonergic receptor subtypes represent a family of drugs with a diversity of therapeutic applications. For example, 5-HT.sub.1 receptor agonists are clinically indicated for anxiety, hypertension and migraine. Selective 5-HT.sub.2 receptor antagonists are marketed as anxiolytics, anti-depressants, anti-hypertensives and appetite stimulants (see 5-HT: The Enigma Variations. J. R. Fozard 1987; Trends. Pharmacol. Sci. 8: 501).
5-HT.sub.3 receptor antagonists are known for their potent antiemetic properties, particularly against emesis induced by cancer chemotherapy and radiotherapy, and for their gastrokinetic activity (see respectively Drugs Acting on 5-Hydroxytryptamine Receptors: The Lancet Sep. 23, 1989 and references cited therein and Reynolds R. C. Prokinetic Agents: A Key in the Future of Gastroenterology. Gastroenterology Clinics of North America 1989; 18: 437-457). In addition, 5-HT.sub.3 receptor antagonists are under investigation for treating CNS diseases involving cognitive dysfunctions, anxiety, dependency disorders and schizophrenia (see article from The Lancet previously cited) and may also be of value in the control of pain, particularly migraine (see Peatfield R. 1988; Drugs and the Treatment of Migraine. Trends, Pharmacol. Sci. 9: 141).
The disclosures of these and other documents referred to throughout this application, e.g., in the Pharmacology section of the Detailed Description of the Invention, are incorporated herein by reference.